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- Zhu, RJ, et al.
(författare)
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Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms
- 2021
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Ingår i: Cell research. - : Springer Science and Business Media LLC. - 1748-7838 .- 1001-0602. ; 31:12, s. 1244-1262
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Tidskriftsartikel (refereegranskat)abstract
- The infusion of coronavirus disease 2019 (COVID-19) patients with mesenchymal stem cells (MSCs) potentially improves clinical symptoms, but the underlying mechanism remains unclear. We conducted a randomized, single-blind, placebo-controlled (29 patients/group) phase II clinical trial to validate previous findings and explore the potential mechanisms. Patients treated with umbilical cord-derived MSCs exhibited a shorter hospital stay (P = 0.0198) and less time required for symptoms remission (P = 0.0194) than those who received placebo. Based on chest images, both severe and critical patients treated with MSCs showed improvement by day 7 (P = 0.0099) and day 21 (P = 0.0084). MSC-treated patients had fewer adverse events. MSC infusion reduced the levels of C-reactive protein, proinflammatory cytokines, and neutrophil extracellular traps (NETs) and promoted the maintenance of SARS-CoV-2-specific antibodies. To explore how MSCs modulate the immune system, we employed single-cell RNA sequencing analysis on peripheral blood. Our analysis identified a novel subpopulation of VNN2+ hematopoietic stem/progenitor-like (HSPC-like) cells expressing CSF3R and PTPRE that were mobilized following MSC infusion. Genes encoding chemotaxis factors — CX3CR1 and L-selectin — were upregulated in various immune cells. MSC treatment also regulated B cell subsets and increased the expression of costimulatory CD28 in T cells in vivo and in vitro. In addition, an in vivo mouse study confirmed that MSCs suppressed NET release and reduced venous thrombosis by upregulating kindlin-3 signaling. Together, our results underscore the role of MSCs in improving COVID-19 patient outcomes via maintenance of immune homeostasis.
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- Jiang, J T, et al.
(författare)
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Treatment of advanced gastric cancer by chemotherapy combined with autologous cytokine-induced killer cells
- 2006
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Ingår i: Anticancer research. - 1791-7530. ; 26:3B, s. 2237-2242
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Tidskriftsartikel (refereegranskat)abstract
- The effects of autologous cytokine-induced killer (CIK) (CD3(+)CD56(+)) cells together with chemotherapy were investigated in patients who suffered from advanced gastric cancers (stage IV). Fifty-seven patients were divided into two groups: chemotherapy plus CIK biotherapy and chemotherapy alone. CIK cells were induced from autologous peripheral blood mononuclear cells in vitro and separated by flow cytometry and then transfused into the patients. The T-lymphocyte subgroups (CD3(+), CD4(+) or CD8(+)), CIK cells and NK cells (CD3(-)CD56(+)) were separated and determined by flow cytometry and the serum levels of MG7-Ag, CA72-4, CA19-9 and CEA were determined by ELISA or ECLIA. It was demonstrated that the cytotoxic activity of CIK cells reached a maximum between days 14 to 21 (68.7 +/- 10.9% and 65.3 +/- 10.4%, respectively). The amounts of CIK cells were gradually increased from day 0 to day 21 and slightly decreased in the further incubations. Thereafter, the CIK cells on days 14 to 21 (with the highest population of CIK cells) transfused back to the patients. The serum levels of the tumor markers were significantly decreased, the host immune function was increased and the short-term curative effect as well as the quality of life (QOL) were improved in the patients treated by chemotherapy plus CIK cells compared to the patients treated by chemotherapy alone. Moreover, the 2-year life-span was prolonged in the group treated by chemotherapy plus CIK cells compared to the group treated with chemotherapy alone. It is concluded that chemotherapy plus CIK cells has obvious benefits for patients who suffer from advanced gastric cancers.
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